Monobasic potassium phosphate → methyl N-(4-{4-[4-(tert-butoxycarbonyl)piperazin-1-yl]phenyl}-3-methylisoxazol-5-yl)leucinate

HRID 1744139Notes

Reaction equation

HRID 1744139 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][C:17]([C:20]3[C:21]([CH3:43])=[N:22][O:23][C:24]=3[N:25](C(OCC(Cl)(Cl)Cl)=O)[C@H:26]([C:31]([O:33][CH3:34])=[O:32])[CH2:27][CH:28]([CH3:30])[CH3:29])=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].OP([O-])(O)=O.[K+]>C1COCC1.[Zn]>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][N:11]([C:14]2[CH:15]=[CH:16][C:17]([C:20]3[C:21]([CH3:43])=[N:22][O:23][C:24]=3[NH:25][C@H:26]([C:31]([O:33][CH3:34])=[O:32])[CH2:27][CH:28]([CH3:30])[CH3:29])=[CH:18][CH:19]=2)[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 2

HCID 516951Monobasic potassium phosphate2×HCID 69151299methyl N-(4-{4-[4-(tert-butoxycarbonyl)piperazin-1-yl]phenyl}-3-methylisoxazol-5-yl)-N-[(2,2,2-trichloroethoxy)carbonyl]leucinate

Product 1

HCID 69153222methyl N-(4-{4-[4-(tert-butoxycarbonyl)piperazin-1-yl]phenyl}-3-methylisoxazol-5-yl)leucinate

Reagents, catalysts & solvents 2

HCID 23994ZincCatalyst2×HCID 8028TetrahydrofuranSolvent

Procedure

To methyl N-(4-{4-[4-(tert-butoxycarbonyl)piperazin-1-yl]phenyl}-3-methylisoxazol-5-yl)-N-[(2,2,2-trichloroethoxy)carbonyl]leucinate (688 mg, 1.04 mmol) in THF (20 mL) was added activated zinc powder (686 mg, 10.4 mmol) and an aqueous solution of KH2PO4 (1.0 M, 5.2 mL, 5.2 mmol) dropwise. After ½ hour additional aliquots of activated zinc powder (686 mg, 10.4 mmol) and aqueous KH2PO4 solution were added (1.0 M, 5.2 mL, 5.2 mmol) and the reaction mixture was stirred for 1 hour. The zinc powder was filtered off, rinsed with Et2O and water and the product extracted with ether (2×), dried over Na2SO4, concentrated iii vacuo and purified by flash chromatography over silica gel (EtOAc/Hex, 3/7) to afford methyl N-(4-{4-[4-(tert-butoxycarbonyl)piperazin-1-yl]phenyl}-3-methylisoxazol-5-yl)leucinate.

Workup

  1. filtrationThe zinc powder was filtered off
  2. washrinsed with Et2O and water
  3. extractionthe product extracted with ether (2×)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated iii vacuo
  6. custompurified by flash chromatography over silica gel (EtOAc/Hex, 3/7)

Sources & evidence

ORD record
ord-344ddd6fff374d9a9de23116f85183f7
Source dataset
uspto-grants-2006_03
Patent number
US07012075B2

Reaction notes

Loading…